Motor patterns for two distinct rhythmic behaviors evoked by excitatory amino acid agonists in the Xenopus embryo spinal cord

1996 ◽  
Vol 75 (5) ◽  
pp. 1815-1825 ◽  
Author(s):  
S. R. Soffe
Keyword(s):  
Amino Acids ◽  
Spinal Cord ◽  
Amino Acid ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Motor Pattern ◽  
Cycle Period ◽  
Motor Patterns ◽  
Sensory Evoked ◽  
Motor Root

1. Mechanisms underlying the selective expression of different motor patterns in vertebrates are poorly understood. Immobilized, spinal Xenopus embryos are used here to examine the motor patterns evoked by various concentrations of excitatory amino acids. 2. Relatively low concentrations of N-methyl-D-aspartate (NMDA) (40-60 microM), kainate (7-8 microM), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (5 microM) evoked motor root discharge characteristic of swimming. Brief applications of higher concentrations of kainate (20-40 microM), AMPA (25-30 microM), quisqualate (5 microM), and glutamate (1-4 mM) evoked sequences of a different motor pattern: struggling. This is characterized by a longer cycle period, increased burst duration, and a reversed longitudinal pattern of motor root discharge. The struggling pattern was never evoked by higher concentrations of NMDA (300-500 microM), but was evoked by 30 microM AMPA or 5 microM quisqualate in the presence of 50 microM D-2-amino-5-phosphonopentanoic acid. 3. Intracellular recordings from presumed spinal motoneurons showed different patterns of activity during agonist-evoked swimming and struggling. The patterns were like those described previously during sensory-evoked behavior. 4. Caudal applications of excitatory amino acids that produced struggling discharge did so only at caudal motor roots, whereas caudal applications of NMDA evoked swimming activity throughout the spinal cord. 5. During excitatory-amino-acid-evoked struggling, sensory Rohon-Beard neurons depolarized up to 7 mV, but did not fire. 6. The results show that expression of the struggling pattern, like swimming, is not critically dependent on sensory discharge. The results are also consistent with the idea that expression of the two very different motor patterns for swimming or struggling in this simple vertebrate preparation can be controlled by the level of excitation within the spinal motor circuitry, and need not involve the activity of a specific external neuromodulator.

Spinal cord excitatory amino acids and cardiovascular autonomic responses

1994 ◽  
Vol 267 (3) ◽  
pp. H865-H873 ◽  
Author(s):  
M. West ◽  
W. Huang
Keyword(s):  
Amino Acids ◽  
Spinal Cord ◽  
Heart Rate ◽  
Amino Acid ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Intrathecal Injection ◽  
Thoracic Spinal Cord ◽  
Upper Thoracic ◽  
Intrathecal Space

The excitatory amino acid subtype receptor agonists, N-methyl-D-aspartate (NMDA) and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, a non-NMDA agonist), produce specific dose-related heart rate and vasoconstrictor responses when given by injection into the upper thoracic or lumbar intrathecal space of the conscious rabbit. The responses are inhibited by prior intrathecal injection of the specific excitatory amino acid subtype receptor antagonist, 2-amino-5-phosphonovaleric acid (AP-5) or 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. Baroreceptor heart rate reflex function is inhibited by AP-5 and by DNQX applied to the upper thoracic spinal cord. In contrast baroreflex vasoconstrictor function is blocked by AP-5 but not by DNQX given in the lumbar intrathecal space. The experiments support previous evidence that spinal excitatory amino acids are important as neurotransmitters at the level of the sympathetic preganglionic neuron and as such exert tonic and reflex control of autonomic cardiovascular function. It is concluded that 1) intrathecal activation of NMDA and non-NMDA subtype receptors has similar but independent effects on heart rate and on blood pressure and 2) NMDA receptors alone participate in mediation of baroreflex vasoconstrictor function, whereas both sets of receptors determine reflex sympathetic heart rate effects.

Amino Acids as Neurotransmitters.: A Symposium to honour Hugh McLennan on his retirement

1991 ◽  
Vol 69 (7) ◽  
pp. 1048-1048
Author(s):  
J. R. Ledsome
Keyword(s):  
Amino Acids ◽  
Spinal Cord ◽  
Amino Acid ◽  
Synaptic Transmission ◽  
Chloride Channels ◽  
Excitatory Amino Acid ◽  
Rapid Development ◽  
Long Term Potentiation ◽  
Isolation And Identification ◽  
University Of British Columbia

A meeting was held at the University of British Columbia on May 28–29, 1990 to honour the many important scientific contributions made by Dr. Hugh McLennan to our understanding of chemical neurotransmission in the brain and spinal cord. The invited speakers were those with whom Dr. McLennan has at one time or another collaborated, and their presentations reflected Hugh's early interest in GÀBA (factor I) as an inhibitory transmitter and his research over the last two decades into the physiology and pharmacology of acidic amino acid receptors.The session on GABA opened with an intriguing discussion by Professor Florey of the history of the isolation and identification of GABA as a neurotransmitter and was followed by papers dealing with the electrophysiological actions of GABA. Professor Curtis discussed its pre- and post-synaptic actions in the spinal cord, while Dr. Mathers presented data derived from GABA-gated chloride channels isolated from cultured neurones. Professor Krnjević was unfortunately unable to attend the symposium.Work presented by Professors Watkins and Lodge and Dr. Curry provided an excellent historical perspective on the birth and rapid development of excitatory amino acid pharmacology, a field to which Dr. McLennan has contributed enormously.Among the topics pertaining to the electrophysiological actions of acidic amino acids was the role of the NMDA receptor both in long-term potentiation (Dr. Collingridge) and in synaptic transmission in the kainic acid-lesioned hippocampus (Dr. Wheal), the effects of antagonists on synaptic transmission in the thalamus (Dr. Hicks), and the modulation by catecholamines of glutamate-induced neuronal excitations (Dr. Marshall).In his closing address Dr. McLennan, with characteristic grace and style, acknowledged the efforts of his co-workers in his many achievements. Those of us who have had the great pleasure of collaborating with Hugh here at UBC or within the scientific community wish him all the best in his retirement.

scholarly journals Roles of Ascending Inhibition During Two Rhythmic Motor Patterns in Xenopus Tadpoles

1998 ◽  
Vol 79 (5) ◽  
pp. 2316-2328 ◽  
Author(s):  
C. S. Green ◽  
S. R. Soffe
Keyword(s):  
Spinal Cord ◽  
Motor Pattern ◽  
Burst Duration ◽  
Major Influence ◽  
Cycle Period ◽  
Detailed Knowledge ◽  
Motor Patterns ◽  
Rhythmic Motor ◽  
Vertebrate Model ◽  
Longitudinal Pattern

Green, C. S. and S. R. Soffe. Roles of ascending inhibition during two rhythmic motor patterns in Xenopus tadpoles. J. Neurophysiol. 79: 2316–2328, 1998. We have investigated the effects of ascending inhibitory pathways on two centrally generated rhythmic motor patterns in a simple vertebrate model, the young Xenopus tadpole. Tadpoles swim when touched, but when grasped respond with slower, stronger struggling movements during which the longitudinal pattern of motor activity is reversed. Surgical spinal cord transection to remove all ascending connections originating caudal to the transection (in tadpoles immobilized in α-bungarotoxin) did not affect “fictive” swimming generated more rostrally. In contrast, cycle period and burst duration both significantly increased during fictive struggling. Increases were progressively larger with more rostral transection. Blocking caudal activity with the anesthetic MS222 (pharmacological transection) produced equivalent but reversible effects. Reducing crossed-ascending inhibition selectively, either by midsagittal spinal cord division or rostral cord hemisection (1-sided transection) mimicked the effects of transection. Like transection, both operations increased cycle period and burst duration during struggling but did not affect swimming. The changes during struggling were larger with more rostral hemisection. Reducing crossed-ascending inhibition by spinal hemisection also increased the rostrocaudal longitudinal delay during swimming, and the caudorostral delay during struggling. Weakening inhibition globally with low concentrations of the glycine antagonist strychnine (10–100 nM) did not alter swimming cycle period, burst duration, or longitudinal delay. However, strychnine at 10–60 nM decreased cycle period during struggling. It also increased burst duration in some cases, although burst duration increased as a proportion of cycle period in all cases. Strychnine reduced longitudinal delay during struggling, making rostral and caudal activity more synchronous. At 100 nM, struggling was totally disrupted. By combining our results with a detailed knowledge of tadpole spinal cord anatomy, we conclude that inhibition mediated by the crossed-ascending axons of characterized, glycinergic, commissural interneurons has a major influence on the struggling motor pattern compared with swimming. We suggest that this difference is a consequence of the larger, reversed longitudinal delay and the extended burst duration during struggling compared with swimming.

Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine

1987 ◽  
Vol 58 (2) ◽  
pp. 251-266 ◽  
Author(s):  
J. F. MacDonald ◽  
Z. Miljkovic ◽  
P. Pennefather
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Aspartic Acid ◽  
Excitatory Amino Acids ◽  
Hippocampal Neurons ◽  
Excitatory Amino Acid ◽  
Outward Current ◽  
Bathing Solution ◽  
Wide Range ◽  
Repeated Applications

1. Mouse hippocampal neurons grown in dissociated cell culture were patch clamped using a whole cell voltage clamp (discontinuous switching clamp) technique. The currents generated by pressure applications of excitatory amino acids were studied over a wide range of holding potentials, and current-voltage curves were plotted. Excitatory amino acids that activated the N-methyl-D-aspartic acid (NMDA) receptor demonstrated some degree of desensitization with repeated applications, whereas the currents observed in response to kainic acid (KAI) did not. Desensitization could be minimized by keeping the frequency of application sufficiently low (i.e., less than 0.1 Hz). 2. The short-acting dissociative anaesthetic, ketamine (2–50 microM), selectively blocked L-aspartic acid (L-Asp), NMDA, and L-glutamic acid (L-Glu) currents while sparing those in response to KAI. Therefore, ketamine is a relatively selective blocker of the NMDA response versus that (those) activated by KAI. 3. The block by ketamine of excitatory amino acid currents is highly voltage dependent. Concentrations of ketamine that had little effect on outward current responses at depolarized potentials were quite effective at blocking inward current responses at hyperpolarized potentials. In contrast, DL-2-amino-5-phosphonovaleric acid (APV) was equally effective at blocking both inward and outward currents (voltage independent). The voltage dependence of ketamine (a positively charged molecule) could be accounted for if ketamine blocked the NMDA response by binding to a site that experienced 55% of the membrane field. 4. In the presence of ketamine, peak inward currents evoked by repeated applications of NMDA, L-Asp, or L-Glu progressively declined to a steady-state level of block (use-dependent block). This decrement occurred at frequencies much lower than those that were employed to demonstrate desensitization (in the absence of ketamine). Moving the membrane potential to depolarized values did not, in itself, relieve the ketamine block. However, if the appropriate excitatory amino acid (L-Asp, NMDA, L-Glu) was applied during the period of depolarization, a relief of the block could be demonstrated. No recovery from the blockade occurred with periods of rest (no amino acid application) as long as 5 min. Furthermore, no recovery was observed even when ketamine was washed out of the bathing solution until the appropriate agonist was applied. Thus recovery from blockade, like development of blockade, was use dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans

1993 ◽  
Vol 79 (3) ◽  
pp. 369-372 ◽  
Author(s):  
Andrew J. Baker ◽  
Richard J. Moulton ◽  
Vernon H. MacMillan ◽  
Peter M. Shedden
Keyword(s):  
Amino Acids ◽  
Traumatic Brain Injury ◽  
Cerebrospinal Fluid ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Neuronal Damage ◽  
Control Group ◽  
Injured Patients

✓ Evidence from models of traumatic brain injury implicates excitotoxicity as an integral process in the ultimate neuronal damage that follows. Concentrations of the excitatory amino acid glutamate were serially measured in the cerebrospinal fluid (CSF) of patients with traumatic brain injuries and in control patients for comparison. The purpose of the study was to determine whether glutamate concentrations were significantly elevated following traumatic brain injury and, if so, whether they were elevated in a time frame that would allow the use of antagonist therapy. Cerebrospinal fluid was sampled fresh from ventricular drains every 12 hours and analyzed using high-performance liquid chromatography for the excitatory amino acids. The peak concentrations of glutamate in the CSF of the 12 brain-injured patients ranged from 14 to 474 µM and were significantly higher than those in the three control patients, 4.9 to 17 µM (Mann-Whitney U-test, p < 0.02). Glutamate concentrations in five of the eight patients who were still being sampled on Day 3 were beyond the control group range. The implication of this study is that severely head-injured patients are exposed to high concentrations of a neurotoxic amino acid for days following injury and thus may benefit from antagonist intervention.

scholarly journals Differential Vulnerability to Excitatory Amino Acid-Induced Toxicity and Selective Neuronal Loss in Neurodegenerative Diseases

1991 ◽  
Vol 18 (S3) ◽  
pp. 394-397 ◽  
Author(s):  
John H. Weiss ◽  
Dennis W. Choi
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Neurodegenerative Diseases ◽  
Excitatory Amino Acids ◽  
Excitatory Amino Acid ◽  
Neuronal Loss ◽  
Intrinsic Vulnerability ◽  
Central Neurons ◽  
Differential Vulnerability

ABSTRACT:Neurodegenerative diseases are characterized by selective degeneration of certain biochemically distinct subpopulations of central neurons. Studies of the intrinsic vulnerability of such neurons to injury by excitatory amino acids in vitro, as well as study of neurologic syndromes produced in animals or humans by ingestion of environmental excitatory amino acid neurotoxins may suggest a link between excitotoxicity, and the pathogenesis of certain neurodegenerative diseases.

Effects of Hypothermia, Pentobarbital, and Isoflurane on Postdepolarization Amino Acid Release during Complete Global Cerebral Ischemia

1996 ◽  
Vol 85 (1) ◽  
pp. 161-168 ◽  
Author(s):  
Ken Nakashima ◽  
Michael M. Todd
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cerebral Ischemia ◽  
Excitatory Amino Acids ◽  
High Performance ◽  
Excitatory Amino Acid ◽  
Protective Efficacy ◽  
Aminobutyric Acid ◽  
Global Cerebral Ischemia ◽  
Gamma Aminobutyric Acid

Background Hypothermia and anesthetics may protect the brain during ischemia by blocking the release of excitatory amino acids. The effects of hypothermia (28 degrees C), pentobarbital, and isoflurane on postischemic excitatory amino acid concentrations were compared. Methods Rats were anesthetized with 0.8% halothane/50% N2O, vascular catheters were placed, and a glass microelectrode and microdialysis cannula were inserted into the cerebral cortex. Experimental groups were: (1) control, pericranial, t = 38 degrees C; (2) hypothermia, t = 28 degrees C; (3) pentobarbital, t = 38 degrees C; and (4) isoflurane, t = 38 degrees C. Halothane/N2O was continued in groups 1 and 2, whereas a deep burst-suppression or isoelectric electroencephalogram was achieved with the test drugs in groups 3 and 4. Cerebral metabolic rates were similar in groups 2, 3, and 4. After a baseline dialysis sample was collected, animals were killed with potassium chloride. The time to terminal depolarization was recorded, after which three consecutive 10-min dialysate samples were collected. Glutamate, aspartate, gamma-aminobutyric acid, and glycine concentrations were measured using high-performance liquid chromatography. Results Times to terminal depolarization were shorter in both pentobarbital and isoflurane groups than with hypothermia (103 +/- 15 and 127 +/- 10 vs. 195 +/- 20 s respectively, mean +/- SD). However, times to terminal depolarization in all three groups were longer than in control subjects (control = 70 +/- 9s). Postdepolarization concentrations of all compounds were lower in hypothermic animals (vs. normothermic control animals), but no reductions in glutamate, aspartate, or glycine concentrations were noted in pentobarbital or isoflurane groups. gamma-Aminobutyric acid concentrations were reduced by both anesthetics, but not to the same degree as with hypothermia. Conclusions Pentobarbital and isoflurane prolonged the time to terminal depolarization, but did not influence the rate at which the extracellular concentrations of glutamate, aspartate, or glycine increased. By contrast, hypothermia reduced the release of all excitatory amino acids. These differences may explain the greater protective efficacy of hypothermia in the face of cerebral ischemia.

scholarly journals Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3049 ◽  
Author(s):  
Valentin A. Stonik ◽  
Inna V. Stonik
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Glutamate Receptors ◽  
Excitatory Amino Acids ◽  
Domoic Acid ◽  
Excitatory Amino Acid ◽  
Biological Action ◽  
Kainate Receptors ◽  
Marine Metabolites ◽  
Structure Properties

This review considers the results of recent studies on marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, known as potent agonists of one of subtypes of glutamate receptors, the so-called kainate receptors. Novel information, particularly concerning biosynthesis, environmental roles, biological action, and syntheses of these marine metabolites, obtained mainly in last 10–15 years, is summarized. The goal of the review was not only to discuss recently obtained data, but also to provide a brief introduction to the field of marine excitatory amino acid research.

Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury

1990 ◽  
Vol 73 (6) ◽  
pp. 889-900 ◽  
Author(s):  
Yoichi Katayama ◽  
Donald P. Becker ◽  
Toru Tamura ◽  
David A. Hovda
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Brain Injury ◽  
Excitatory Amino Acids ◽  
Kynurenic Acid ◽  
Excitatory Amino Acid ◽  
Maximum Effect ◽  
Receptor Subtypes ◽  
Severity Of Injury

✓ An increase in extracellular K+ concentration ([K+]e) of the rat hippocampus following fluid-percussion concussive brain injury was demonstrated with microdialysis. The role of neuronal discharge was examined with in situ administration of 0.1 mM tetrodotoxin, a potent depressant of neuronal discharges, and of 0.5 to 20 mM cobalt, a blocker of Ca++ channels. While a small short-lasting [K+]e increase (1.40- to 2.15-fold) was observed after a mild insult, a more pronounced longer-lasting increase (4.28- to 5.90-fold) was induced without overt morphological damage as the severity of injury rose above a certain threshold (unconscious for 200 to 250 seconds). The small short-lasting increase was reduced with prior administration of tetrodotoxin but not with cobalt, indicating that neuronal discharges are the source of this increase. In contrast, the larger longer-lasting increase was resistant to tetrodotoxin and partially dependent on Ca++, suggesting that neurotransmitter release is involved. In order to test the hypothesis that the release of the excitatory amino acid neurotransmitter glutamate mediates this increase in [K+]e, the extracellular concentration of glutamate ([Glu]e) was measured along with [K+]e. The results indicate that a relatively specific increase in [Glu]e (as compared with other amino acids) was induced concomitantly with the increase in [K+]e. Furthermore, the in situ administration of 1 to 25 mM kynurenic acid, an excitatory amino acid antagonist, effectively attenuated the increase in [K+]e. A dose-response curve suggested that a maximum effect of kynurenic acid is obtained at a concentration that substantially blocks all receptor subtypes of excitatory amino acids. These data suggest that concussive brain injury causes a massive K+ flux which is likely to be related to an indiscriminate release of excitatory amino acids occurring immediately after brain injury.

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